FDA Type B Meeting Elucidates Testosterone-Associated Breast Cancer Risks

The FDA has provided guidance through a Type B meeting on the use of testosterone therapy in women, citing the use of AVA-291 (d3-T) as a next-generation testosterone that is designed to retain testosterone androgen activity while resisting aromatization, according to a press release from Aviva Bio.¹

A potential risk of breast cancer has been noted with the use of testosterone in women, and the FDA highlighted that concern during the meeting. Through molecular design and evidence-based strategies, d3-T’s developer will continue to address this risk.

Developers designed D3-T as a novel deuterium-substituted isotopologue of testosterone, which can resist aromatization. Of note, the aromatization of d3-T is linked with potential safety concerns for breast cancer and tolerability concerns for gynecomastia. In human studies, d3-T was found to be a direct substitute for ordinary testosterone.

Data regarding the use of d3-T has been accepted to the 2026 American Association for Cancer Research Annual Meeting. Results show a 1000-fold potential of d3-T to reduce breast cancer cell proliferation compared with standard testosterone.

Additionally, d3-T has similar physical properties to testosterone and can be substituted in any testosterone formulation. The developers noted that the agent may serve as an alternative in situations where the aromatization associated with standard testosterone limits its therapeutic potential. These situations include hormone replacement therapy among women who are menopausal, men receiving testosterone therapy who experience gynecomastia, patients receiving GLP-1 therapy who develop muscle loss and/or low libido, and those with estrogen receptor–positive breast cancer.

Developers continue to advance d3-T as a differentiated form of testosterone for multiple indications in women’s and men’s health where androgen signaling may play a significant role.

“For decades, testosterone therapy for women has depended on repurposed male formulations, rather than drugs designed with women’s biology and safety considerations in mind,” Judith A. Boice, PhD, chief executive officer of Aviva Bio, said in the press release.¹ “Our FDA feedback reinforces the need for a new standard—one anchored in safety, enabled by molecular precision, and developed with regulatory clarity from the start.”

In addition to Boice’s comments, Bradford C. Sippy, chief technical officer at Aviva Bio, noted that d3-T has provided mechanistic evidence of breast cancer reduction compared with standard testosterone.¹

At the 2025 Endocrine Society Annual Meeting, results for d3-T were presented.² Key findings showed that d3-T was resistant to aromatization, which was demonstrated across multiple studies. In inducing androgen receptor activation, d3-T was determined to be equally potent and efficacious when compared with testosterone. Similar metabolic stability and metabolite production were noted with d3-T vs testosterone in both human and animal models.

The press release on the updated data noted that d3-T resists aromatization, which is the metabolic process driving the conversion of androgens to estradiol. Because of this, estradiol-driven adverse effects like breast cancer and gynecomastia may be reduced with the use of d3-T.

“This is a pivotal moment addressing a significant unmet need in women’s health,” Barbara S. Levy, MD, FACOG, FACS, chief medical officer at Visana Health Inc. and clinical professor of Obstetrics and Gynecology at The George Washington University School of Medicine and Health Sciences, said in a press release.² “d3-T could significantly enhance options for hormone therapy in menopausal and perimenopausal women.”

In the 2025 press release, the developers noted that a phase 1 trial was being prepared to launch in early 2026.

References

1. Aviva Bio announces FDA guidance on development pathway for women’s testosterone therapy and new evidence of a reduced risk of breast cancer cell proliferation for AVA-291. News release. Aviva Bio. January 26, 2026. Accessed January 26, 2026. https://tinyurl.com/3ujz2nfn
2. Aviva Biopharm Inc. unveils groundbreaking pre-clinical data on d3-T, a first-in-class testosterone therapy for women at ENDO 2025. News release. Aviva Bio. July 14, 2025. Accessed January 26, 2026. https://tinyurl.com/36yw9fwz